Humanin (10mg)

Humanin Peptide

Humanin is a short natural peptide with suggested potential in cell metabolism and inflammation responses.⁽³⁾ A mitochondrial genome called ‘16S ribosomal RNA gene’ is suggested by researchers to encode the Humanin peptide.⁽⁴⁾ Researchers further posit that the peptide's length may depend on its synthesis's location. The peptide may contain 21 amino acids if synthesized inside the mitochondria, whereas it may contain 24 amino acids if synthesized outside mitochondria but inside the cytosol.⁽⁵⁾ Both of these peptides exhibit potential biological activity.

Mitochondria, considered the cell's powerhouse, is formed from the engulfment of individual prokaryotes. The eukaryotes, at some point, appear to engulf the prokaryotic (single celled) organism where the prokaryotes form an endosymbiotic relation with the host cell and gradually develop into mitochondria.⁽¹⁾

Mitochondria is suggested to be responsible for several vital cellular activities including production of energy, regulation of apoptosis, hemostasis, and formation of heme proteins, among several other functions. All these functions appear to be regulated by mitochondria via its communications to the cell through several retrograde signals. These signals may be encoded by the nuclear genome present in the mitochondria, possibly due to its prokaryotic origin.⁽²⁾

A small peptide is derived from this genome called Humanin. Since this genome appears to play such an important role, this peptide has been explored for its potential action in several biological functions.

Overview

The peptide appears to exerts some potential via binding with intracellular molecules and cell membrane receptors, thereby possibly inducing cytoprotective and/or neuroprotective functions.⁽⁹⁾ Researchers suggest that Humanin may bind with the Bcl-2 associated X protein (also called Bax protein). Bax protein is considered to play a vital role in cellular death (apoptosis). Upon binding with the inactive form of the Bax protein, Humanin may inhibit the changes in the Bax protein and potentially thereby prevent cellular apoptosis.⁽⁹⁾

Apart from research into its possible interaction with Bax, Humanin studies suggest the peptide may also bind with other intracellular molecules such as actinin-4 and phosphoprotein 8, which are both involved in cellular apoptosis. Upon binding with these proteins, Humanin may induce cytoprotective actions. Researchers suggest Humanin may possibly bind with two G protein coupled peptide receptors, namely FPRL-1 and FPRL-2 receptors, which are considered to be involved with neurological function.⁽⁹⁾ By binding with this receptor, Humanin may potentially prevent amyloid β binding with the FPRL-1 and FPRL-2 receptors, which may mitigate some instances of neurological degradation.

Research and Clinical Studies

Humanin Peptide and Mitochondrial Functions

Mitochondria appears to be susceptible in reactive oxygen species (ROS) the presence of which may reduce its functioning. Studies in Humanin mechanisms of action suggest that the peptide may inhibit to some degree these reactive oxygen species and thereby mitigate mitochondria degeneration.⁽¹⁰⁾ One study was produced wherein the researchers attempted to explore the peptide's action on retinal pigment epithelial cells. These cells were isolated and introduced to tert-butyl hydroperoxide to exert oxidative stress in the cells. Some of these cells were then presented with Humanin peptide for a period of 24 hours. When examined, the Humanin

cells reportedly inhibited formation of tert-butyl hydroperoxide induced reactive oxygen species. The researchers suggested the peptide may have restored the bioenergetics in the retinal pigment epithelial cells and increased the functioning of mitochondria.

Humanin Peptide and Cellular Longevity

Studies⁽¹¹⁾ were conducted on several mice models to determine the relation between Humanin with growth hormone (GH) and immunoglobulin (IGF-1). In GH-transgenic mice, the levels of growth hormones and IGF-1 appeared to be extremely high, which the researchers suggested lead to an increased body size, accelerated aging, and reduced life span. Researchers reported that the levels of Humanin naturally present in the mice models were extremely low, by and average of -70% reduction compared to control.

In the other model of Ames mice, they consisted of mutated prop-1 gene, which had undetectable levels of GH and IGF-1, along with a reported 40% increase in the Humanin levels. These mice showed an increased life span compared to normal mice. These results supported the hypothesis the researchers presented, which was that Humanin may be negatively correlated to GH and IGF-1 levels and directly correlated to cellular longevity.

Humanin Peptide and Neurological Deterioration

A study⁽¹²⁾ was conducted where a 9-month-old mice model was employed, of which all reportedly possessed high levels of amyloid proteins. These amyloid chemicals are indicative of some neurological deterioration. Some of these mice were presented with Humanin and the others were given a placebo. Following the study, it was suggested by the researchers that the placebo mice showed impaired memory and poor learning skills, whereas the mice presented with Humanin for 3 months reportedly exhibited significantly improved learning ability and enhanced memory.

In another study,⁽¹³⁾ experimentally induced mice with reported impaired neurological functioning were introduced with Humanin and a similarly structured peptide called PAGA, to determine the potential of both peptides on the brain function of the mice. Both the peptides showed some modest improvement in the impairment of the brain, researchers suggested.

Humanin Peptide and Insulin Resistance

In order to determine the potential of Humanin on insulin resistance, a study⁽¹⁴⁾ was conducted on nonobese diabetic mice. When a group of these mice were presented with Humanin, it appeared to restore to some degree the levels of glucose tolerance within 6 weeks. Furthermore, Humanin also reportedly delayed the onset of diabetes in the mice presented with the peptide for 20 weeks. Researchers suggested that following the study results, that Humanin may exhibit some action in insulin resistance.

In another study,⁽¹⁵⁾ 12-week-old mice were subjected to a 60% high fat diet and were presented with Humanin for 4 weeks. After the study, there appeared to be no difference in the food intake, however, the body weight gain had reportedly been reduced by about 20%. Furthermore, there appeared to be a high expenditure of energy and decreased levels of fasting glucose, in addition to increased insulin levels.

Humanin Peptide and Hypoxia

A study⁽¹⁶⁾ was conducted where the isolated retinal cells were given cobalt chloride, which appeared to induce hypoxia leading towards cell apoptosis. When the hypoxia induced cells were presented with Humanin, researchers reported that the peptide appeared to reverse the impact of cobalt chloride and protect the cell from reduced oxygen levels.

Additional studie⁽¹⁷⁾ have suggested that Humanin may possibly increase metabolic activity and thereby possibly cell survival rates, in the event of death of lymphocytes, which has some implication in ischemia.

Humanin Peptide and Ischemia

This study⁽¹⁸⁾ was conducted to further examine the neuroprotective potential of Humanin in the presence of cerebral ischemia. As a part of this study, mice were experimentally induced with cerebral artery occlusion. Mice were presented with low concentrations of Humanin for 30 minutes and then following the procedure were reintroduced to Humanin at  0, 2, 4 and 6 hours after ischemia. Other mice were solely presented with Humanin one hour prior to ischemia. It was suggested that continual introduction to the peptide appeared to reduce the ischemia volume by almost 30%. Humanin presence following ischemia reportedly further reduced the ischemic impact.

Humanin Peptide Additional Studies

Studies⁽¹⁹⁾ have suggested that Humanin may bind with the FPR2 receptor in the brain which may lead to producing anxiolytic action. Consequently, the researchers of this study suggested that Humanin may reduce symptoms of anxiety.

In this study,⁽²⁰⁾ carcinogenic mice were induced twice per week with Bortezomib and Humanin to explore their potential impact on the carcinogenic cells. While Bortezomib appeared to induce cell apoptosis, Humanin and Bortezomib combination exhibited some potential, somewhat reversing the apoptosis of the healthy cells.

Humanin peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering.

References:

1. The origin of mitochondria and chloroplasts. https://www.nature.com/scitable/content/the-origin-of-mitochondria-and-chloroplasts-14747702/
2. Lee, Changhan et al. “Humanin: a harbinger of mitochondrial-derived peptides?.” Trends in endocrinology and metabolism: TEM vol. 24,5 (2013). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641182/
3. Gong, Zhenwei et al. “Humanin and age-related diseases: a new link?.” Frontiers in endocrinology vol. 5 210. 4 Dec. 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255622/
4. Hashimoto Y, Niikura T, Tajima H, Yasukawa T, Sudo H, Ito Y, Kita Y, Kawasumi M, Kouyama K, Doyu M, Sobue G, Koide T, Tsuji S, Lang J, Kurokawa K, Nishimoto I. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta. Proc Natl Acad Sci U S A. 2001 May 22;98(11):6336-41. https://pubmed.ncbi.nlm.nih.gov/11371646/
5. Yen K, Lee C, Mehta H, Cohen P. The emerging role of the mitochondrial-derived peptide humanin in stress resistance. J Mol Endocrinol. 2013 Jan 11;50(1):R11-9. https://pubmed.ncbi.nlm.nih.gov/23239898/
6. Gong, Zhenwei et al. “Humanin and age-related diseases: a new link?.” Frontiers in endocrinology vol. 5 210. 4 Dec. 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255622/
7. Guo B, Zhai D, Cabezas E, Welsh K, Nouraini S, Satterthwait AC, Reed JC. Humanin peptide suppresses apoptosis by interfering with Bax activation. Nature. 2003 May 22;423(6938):456-61. https://pubmed.ncbi.nlm.nih.gov/12732850/
8. Ikonen M, Liu B, Hashimoto Y, Ma L, Lee KW, Niikura T, Nishimoto I, Cohen P. Interaction between the Alzheimer's survival peptide humanin and insulin-like growth factor-binding protein 3 regulates cell survival and apoptosis. Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13042-7. https://pubmed.ncbi.nlm.nih.gov/14561895/
9. Gong, Zhenwei et al. “Humanin and age-related diseases: a new link?.” Frontiers in endocrinology vol. 5 210. 4 Dec. 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255622/
10. Sreekumar PG, Ishikawa K, Spee C, Mehta HH, Wan J, Yen K, Cohen P, Kannan R, Hinton DR. The Mitochondrial-Derived Peptide Humanin Protects RPE Cells From Oxidative Stress, Senescence, and Mitochondrial Dysfunction. Invest Ophthalmol Vis Sci. 2016 Mar;57(3):1238-53. https://pubmed.ncbi.nlm.nih.gov/26990160/
11. Changhan Lee et al, IGF-I regulates the age-dependent signaling peptide humanin. Published 18 July 2014, Vol 13 Issue 5. https://onlinelibrary.wiley.com/doi/full/10.1111/acel.12243
12. Zhang W, Zhang W, Li Z, Hao J, Zhang Z, Liu L, Mao N, Miao J, Zhang L. S14G-humanin improves cognitive deficits and reduces amyloid pathology in the middle-aged APPswe/PS1dE9 mice. Pharmacol Biochem Behav. 2012 Jan;100(3):361-9. https://pubmed.ncbi.nlm.nih.gov/21993310/
13. Krejcova G, Patocka J, Slaninova J. Effect of humanin analogues on experimentally induced impairment of spatial memory in rats. J Pept Sci. 2004 Oct;10(10):636-9. https://pubmed.ncbi.nlm.nih.gov/15526713/
14. Hoang PT, Park P, Cobb LJ, Paharkova-Vatchkova V, Hakimi M, Cohen P, Lee KW. The neurosurvival factor Humanin inhibits beta-cell apoptosis via signal transducer and activator of transcription 3 activation and delays and ameliorates diabetes in nonobese diabetic mice. Metabolism. 2010 Mar;59(3):343-9. https://pubmed.ncbi.nlm.nih.gov/19800083/
15. Zhenwei Gong et al, Central effects of humanin on hepatic triglyceride secretion, Endocrinology and Metabolism. https://journals.physiology.org/doi/full/10.1152/ajpendo.00043.2015
16. Men J, Zhang X, Yang Y, Gao D. An AD-related neuroprotector rescues transformed rat retinal ganglion cells from CoCl₂-induced apoptosis. J Mol Neurosci. 2012 May;47(1):144-9. doi: 10.1007/s12031-011-9701-5. Epub 2012 Jan 5. https://pubmed.ncbi.nlm.nih.gov/22222604/
17. Kariya S, Takahashi N, Hirano M, Ueno S. Humanin improves impaired metabolic activity and prolongs survival of serum-deprived human lymphocytes. Mol Cell Biochem. 2003 Dec;254(1-2):83-9. https://pubmed.ncbi.nlm.nih.gov/14674685/
18. Xu X, Chua CC, Gao J, Hamdy RC, Chua BH. Humanin is a novel neuroprotective agent against stroke. Stroke. 2006 Oct;37(10):2613-9. Epub 2006 Sep 7. https://pubmed.ncbi.nlm.nih.gov/16960089/
19. Zhao H, Sonada S, Yoshikawa A, Ohinata K, Yoshikawa M. Rubimetide, humanin, and MMK1 exert anxiolytic-like activities via the formyl peptide receptor 2 in mice followed by the successive activation of DP1, A2A, and GABAA receptors. Peptides. 2016 Sep;83:16-20. https://pubmed.ncbi.nlm.nih.gov/27475912/
20. Emma Eriksson, Malin Wickström, Lova Segerström Perup, John I. Johnsen, Staffan Eksborg, Per Kogner, Lars Sävendahl, Protective Role of Humanin on Bortezomib-Induced Bone Growth Impairment in Anticancer Treatment, JNCI: Journal of the National Cancer Institute, Volume 106, Issue 3, March 2014, djt459, https://doi.org/10.1093/jnci/djt459